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LENS & CATARACT
Prof. Naimatullah Khan Kundi
Head, Department of Ophthalmology
Khyber Teaching Hospital
Peshawar
Lens & Cataract

(Biochemistry)

 Molecular Biology


Lens proteins conc. 33% structural proteins



Fibers Proteins:

1. Crystallins - Water soluble group 86% (a, b, r)
2. Water insoluble fraction
Lens & Cataract

(Biochemistry)

 Molecular Biology


Crystallins: Intracellular (within the plasma membrane of the
lens epithelium and fiber cells)



Water insoluble fraction associated with fiber plasma
membranes



Brown cataract (Brunescent) – Amount of insoluble proteins correlate with
degree of opacification (90% of nuclear proteins insoluble)
Lens & Cataract

(Biochemistry)

 Carbohydrate Metabolism
 Glucose – (hexokinase)



G6P – Enters



Anaerobic Glycolysis



Pentose Phosphate Pathway / HMP shunt
Lens & Cataract

(Biochemistry)

 Carbohydrate Metabolism


Anaerobic Glycolysis:



More active



Provides most of the high energy phosphate bonds for
lens metabolism
Lens & Cataract

(Biochemistry)

 Carbohydrate Metabolism


HMP Shunt / Pentose phosphate pathway:



Less active pathway of G6P utilization in the lens



5% of lens glucose metabolized by this route



This pathway stimulated in the presence of high levels of
glucose
Lens & Cataract

(Biochemistry)

 Carbohydrate Metabolism (Cont’d)
 Sorbital pathway


Aldose reductase has a key role in the development of
sugar cataract



Normally < 4 % of lens glucose converted to sorbital



When glucose increased in the lens, sorbital pathway
activated relatively more than glycolysis and sorbital
accumulates
Lens & Cataract

(Biochemistry)

 Carbohydrate Metabolism (Cont’d)
 Sorbital pathway (Cont’d)


Sorbital – s. dehydrogenese  fructose:



(This enzyme has low afinity, hence sorbital
accumulates + poor permeability of the lens to
sorbital)
Lens & Cataract

(Biochemistry)

 Carbohydrate Metabolism (Cont’d)
 Sorbital pathway (Cont’d)
 Sorbital + Fructose:


Increased Osmotic pressure within the lens, drawing
in water



Energy dependent pumps of the lens are
overwhlemed



Result: Lens fibers swelling  disruption of the
normal cytoskeletal architecture  lens
Lens & Cataract

(Biochemistry)

 Carbohydrate Metabolism (Cont’d)


Galactose



Galactose is also substrate for aldose reductase
producing galactital (Dulcitol)



Galactose is not substrate for alcohol dehydrogenese
and thus rapidly accumulates
Lens & Cataract

(Biochemistry)

 Oxidative Damage and Protective
Mechanisms
 Free radicles generated as a result of:
 Normal metabolic activities
 External agents (Radiant energy)
Lens & Cataract

(Biochemistry)

 Oxidative Damage and Protective
Mechanisms
 These highly free radicles damage the lens fibers
 Oxygen tension in the lens decreases,
 So free radicles may not involve molecular
oxygen

 Instead the free radicles may react directly with
molecules
Lens & Cataract

(Biochemistry)

 Oxidative Damage and Protective
Mechanisms
Protective lens enzymes against free radicles /
oxygen damage:

 Glutathione peroxidase
 Catalase
 Superoxide Dimutase
 Vit. E & C present in the lens also protect against
damage (free radicle scavengers)
Ophthalmologicical Biochemistry

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Ophthalmologicical Biochemistry

  • 1. LENS & CATARACT Prof. Naimatullah Khan Kundi Head, Department of Ophthalmology Khyber Teaching Hospital Peshawar
  • 2. Lens & Cataract (Biochemistry)  Molecular Biology  Lens proteins conc. 33% structural proteins  Fibers Proteins: 1. Crystallins - Water soluble group 86% (a, b, r) 2. Water insoluble fraction
  • 3. Lens & Cataract (Biochemistry)  Molecular Biology  Crystallins: Intracellular (within the plasma membrane of the lens epithelium and fiber cells)  Water insoluble fraction associated with fiber plasma membranes  Brown cataract (Brunescent) – Amount of insoluble proteins correlate with degree of opacification (90% of nuclear proteins insoluble)
  • 4. Lens & Cataract (Biochemistry)  Carbohydrate Metabolism  Glucose – (hexokinase)  G6P – Enters  Anaerobic Glycolysis  Pentose Phosphate Pathway / HMP shunt
  • 5. Lens & Cataract (Biochemistry)  Carbohydrate Metabolism  Anaerobic Glycolysis:  More active  Provides most of the high energy phosphate bonds for lens metabolism
  • 6. Lens & Cataract (Biochemistry)  Carbohydrate Metabolism  HMP Shunt / Pentose phosphate pathway:  Less active pathway of G6P utilization in the lens  5% of lens glucose metabolized by this route  This pathway stimulated in the presence of high levels of glucose
  • 7. Lens & Cataract (Biochemistry)  Carbohydrate Metabolism (Cont’d)  Sorbital pathway  Aldose reductase has a key role in the development of sugar cataract  Normally < 4 % of lens glucose converted to sorbital  When glucose increased in the lens, sorbital pathway activated relatively more than glycolysis and sorbital accumulates
  • 8. Lens & Cataract (Biochemistry)  Carbohydrate Metabolism (Cont’d)  Sorbital pathway (Cont’d)  Sorbital – s. dehydrogenese  fructose:  (This enzyme has low afinity, hence sorbital accumulates + poor permeability of the lens to sorbital)
  • 9. Lens & Cataract (Biochemistry)  Carbohydrate Metabolism (Cont’d)  Sorbital pathway (Cont’d)  Sorbital + Fructose:  Increased Osmotic pressure within the lens, drawing in water  Energy dependent pumps of the lens are overwhlemed  Result: Lens fibers swelling  disruption of the normal cytoskeletal architecture  lens
  • 10. Lens & Cataract (Biochemistry)  Carbohydrate Metabolism (Cont’d)  Galactose  Galactose is also substrate for aldose reductase producing galactital (Dulcitol)  Galactose is not substrate for alcohol dehydrogenese and thus rapidly accumulates
  • 11. Lens & Cataract (Biochemistry)  Oxidative Damage and Protective Mechanisms  Free radicles generated as a result of:  Normal metabolic activities  External agents (Radiant energy)
  • 12. Lens & Cataract (Biochemistry)  Oxidative Damage and Protective Mechanisms  These highly free radicles damage the lens fibers  Oxygen tension in the lens decreases,  So free radicles may not involve molecular oxygen  Instead the free radicles may react directly with molecules
  • 13. Lens & Cataract (Biochemistry)  Oxidative Damage and Protective Mechanisms Protective lens enzymes against free radicles / oxygen damage:  Glutathione peroxidase  Catalase  Superoxide Dimutase  Vit. E & C present in the lens also protect against damage (free radicle scavengers)